Masanobu Akagi

Inhibition of stress-induced gastric injury in the rat by glutathione

Glutathione metabolism occurs via interorgan cycles in which hepatic synthesis of reduced glutathione and its transfer to extrahepatic tissues play an important role. To elucidate the physiologic significance of the cycles and tissue thiol status during stress-induced gastric mucosal injury, dynamic aspects of glutathione metabolism were analyzed in rats that were treated with water-immersion restraint. This treatment induced gastric mucosal lesion with concomitant decrease in the levels of perchloric acid-soluble thiols in various tissues, particularly in the liver and stomach. During the treatment, glutathione levels markedly decreased in the liver but not in other tissues. Depletion of hepatic glutathione by buthionine sulfoximine, a specific inhibitor for gamma-glutamyl cysteine synthetase, markedly decreased hepatic glutathione levels and increased the gastric injury. Intraperitoneal injection of reduced glutathione significantly increased plasma levels of glutathione and inhibited the occurrence of gastric injury without affecting intracellular glutathione levels. These results indicate that extracellular glutathione and its interorgan metabolism might play a critical role in the protection of gastric mucosa particularly when animals were challenged with various stress.

Evaluation of Serum CA125 Values in Healthy Individuals and Pregnant Women

CA125 is an antigenic determinant associated with human epithelial ovarian carcinoma. This study was undertaken to evaluate the distribution of serum CA125 levels and the effect of smoking on these levels among healthy individuals and clarify the relation of maternal serum CA125 level and pregnancy. Among 552 healthy individuals, the distribution of serum CA125 values was demonstrated to resemble logarithmic normal distribution. Analysis of variance about age and sex revealed apparent elevation of values for women under 49 years of age in comparison with those for women over 50 years of age and men. Values for these two groups were 143 units/ml for the former and 32 units/ml for the latter, with a 99.7% confidence limit. These values exclude 99.3% of the former and 99.7% of the latter. Serum CA125 values were not affected by smoking. The measurement of serum CA125 levels in 71 pregnant women disclosed a significant elevation during the first trimester in comparison with non-pregnant women under 49 years of age. These results indicate that CA125 values must be deliberatively evaluated in young women, especially during first trimester of pregnancy.

Clinical Significance of Serum CA125 Values in Patients with Cancers of the Digestive System

A study of 347 patients with gastrointestinal diseases revealed elevation of CA125 in sera of 63% of patients with pancreatic carcinoma, 46% of patients with carcinoma of the biliary tract, 40% of patients with liver carcinoma and 11–37% of patients with other carcinomas. All of the patients with acute pancreatitis, chronic pancreatitis, cholelithiasis, and peptic ulcer had normal CA125 values, but 35% of patients with liver cirrhosis and 10% of patients with chronic active hepatitis had elevated values. Patients with disseminated carcinomas had significantly higher levels than patients with localized carcinomas. CA125 did not significantly correlate with CA19–9 or carcino-embryonic antigen in patients with pancreatic carcinoma. Ninety-seven percent of patients with pancreatic carcinoma were defined as being positive when both serum CA125 and CA19–9 were evaluated. These results indicate that CA125 is useful for differentiating pancreatic carcinoma from chronic pancreatitis, especially when supplemented with CA19–9.

Definition of carcinoma of the gastric cardia.

ZusammenfassungDiese Untersuchung befaßt sich mit der Definition von Carcinomen der Kardia. An 182 Patienten, die weder Hiatushernien, Ulcera noch Neoplasien des Oesophagus bzw. des Magens aufwiesen, wurde die Lage des Übergangs von der Oesophagus- zur Magenmucosa (esophagogastric mucosal junction, EGJ) endoskopisch untersucht. Dann wurde die Beziehung zwischen EGJ und dem Drüsengebiet der Kardia histologisch anhand von 56 Resektaten mit intaktem EGJ und Kardiadrüsenzone untersucht. Außerdem wurde an 102 resezierten Carcinomen mit Sitz in der Nähe des gastrooesophagealen Übergangs die kürzeste Ent fernung zwischen Carcinomzentrum und EGJ und das Ausmaß der Oesophagusinfiltration bestimmt; die Proben schlossen den EGJ ein und konnten pathohistologisch beurteilt werden. Bei der radiologischen und endoskopischen Untersuchung fand sind der EGJ 0,5–1,0 cm vom His-Winkel entfernt. Die histologische Untersuchung zeigte, daß die Kardiadrüsenzone sich vom EGJ etwa 1 cm nach proximal und 2 cm nach distal erstreckt. Die meisten Tumoren des oberen Magens (87,5%), deren Zentrum innerhalb von 2 cm vom EGJ entfernt lag, infiltrierten in den Oesophagus. Ein Kardiacarcinom ist demzufolge als Läsion zu definieren, deren Zentrum innerhalb von 1 cm proximal und 2 cm distal des EGJ liegt.SummaryThis study concerns the definition of carcinoma of the gastric cardia. The topography of the esophagogastric mucosal junction (mucosal EGJ) was investigated with an endoscope in 182 patients who were free of hiatal hernias, ulcers, and neoplasms in the esophagus and stomach. The relationship between the EGJ and the cardiac gland area was then examined histologically in 56 resected specimens containing intact EGJs and cardia gland areas. Furthermore the cancerous center was determined; the shortest distance between the cancerous center and the EGJ and the amount of esophageal invasion were measured in 102 resected carcinomas located close to the junction; the carcinomas contained the EGJ and were good enough for pathohistological examination. The EGJ was located 0.5–1.0 cm proximal to the His angle (the gastric cardia) in radiological and endoscopic examinations. Histologically the cardiac gland area was found to straddle the EGJ at a range of about 1 cm proximal and 2 cm distal to the junction. Among the upper stomach carcinomas, most of the tumors (87.5%) whose center was located within 2 cm from the EGJ invaded the esophagus. In conclusion, carcinoma of the gastric cardia is defined as a lesion with its center located within 1 cm proximal and 2 cm distal to the EGJ.

Randomized adjuvant trial to evaluate the addition of tamoxifen and PSK to chemotherapy in patients with primary breast cancer: 5‐year results from the nishi‐nippon group of the adjuvant chemoendocrine therapy for breast cancer organization

Background. A randomized adjuvant trial was conducted from October 1982 to January 1985 to evaluate the addition of tamoxifen (TAM) to combination chemotherapy with perioperative mitomycin C (MMC) and ftorafur (FT) for patients with estrogen receptor (ER)‐positive tumors and the addition of PSK, a biologic response modifier, to MMC + FT chemotherapy for patients with ER‐negative tumors in operable Stage IIA, IIB, and IIIA cancer. The doses used were 20 mg of oral TAM daily, 600 mg of oral FT daily, and 3 g of oral PSK daily for 2 years. Intravenous MMC (13 mg/m2) was given on the day of operation.

Intrahepatic Ramification of the Portal Vein in the Right and Caudate Lobes of the Liver

We defined the subsegmental divisions and the ramification patterns of the portal vein in the right and caudate lobes using 25 human liver casts. The ramifications of the portal vein and the subdivisions of the liver were classified based on the major portal veins with the largest diameter and those having a diameter of not less than two thirds of the largest vein in each subsegment. The following results were obtained. (1) The portal trunk showed three ramification patterns and the basic pattern was bifurcation (80%). (2) The anterior portal vein first ramified into several anterior-inferior portal veins (P5) and ran toward the superior direction to bifurcate into 2 major portal veins in the anterior-superior subsegment (S8). (3) There were three types of ramification patterns of the portal veins in S8: bifurcation (84%), trifurcation and one-pedicle type. (4) There were also three branching types of the largest vein (P5-max) in P5: ramification from the anterior portal vein, P8-anterior vein supplying the anterior region of S8 and P8-posterior vein supplying the posterior region of S8. (5) The posterior portal vein showed two ramification patterns of the bifurcation (36%) and nonbifurcation type. (6) The major portal veins in the caudate subsegment ramified at various sites such as the portal trunk, left, right and/or other portal veins.

Zinc clearance correlates with clinical severity of Crohn's disease

After peroral and intravenous loading of zinc in 10 patients with Crohns disease, a kinetic analysis of serum zinc was carried out. The patients were divided into two groups depending on the clinical activity indices (group A: five with active form and group B: five with inactive form). The mean level of serum zinc was significantly reduced in group A patients, but not in group B, when compared to findings in control subjects. A significant reduction in AUCpo (area under the concentration vs time curve by peroral administration), accompanied by increased zinc clearance (ClZn) was also found in group A but not in group B. The ClZn significantly correlated with clinical activity indices. Absorption efficiency, the ratio of AUCpo/AUCiv (area under the concentration vs time curve by intravenous administration), was similar in group A, group B, and the control. Therefore, the absorption of zinc in patients with the disease seems to be intact, regardless of whether they have the active or inactive form of Crohns disease. The hypozincemia seen in patients with Crohns disease is presumably related to an accelerated turnover rather than to a malabsorption of zinc.

Intracellular accumulation of cholesteryl esters suppresses production of lipopolysaccharide-induced interleukin 1 by rat peritoneal macrophages

Interleukin 1 (IL-1) is a major cytokine of macrophages secreted by several stimulants such as lipopolysaccharide (LPS). Macrophages are known to possess the scavenger receptor for acetylated low density lipoprotein (acetyl-LDL) and maleylated albumin. In the present study we determined effects of these ligands on LPS-induced IL-1 production by rat peritoneal macrophages. These ligands themselves did not induce IL-1 production. However, upon short incubation with acetyl-LDL, LPS-induced IL-1 production was significantly suppressed. The extent of the suppression was proportional to cellular cholesteryl esters. Thus, intracellular accumulation of cholesteryl esters might be responsible for suppression of LPS-induced IL-1 production.

Antigen Reversion of Glycogen Phosphorylase Isoenzyme in Carcinoma and Proliferative Zone of Intestinal Metaplasia of the Human Stomach

Specific antibodies to three purified glycogen phosphorylase isoenzymes, i.e., brain (or fetal), muscle, and liver types, were used to study the localization of these isoenzymes in carcinoma and the proliferative zone of intestinal metaplasia of the human stomach. Both the malignant cells of well-differentiated adenocarcinoma and the proliferative zone of some intestinal metaplasia of the stomach were stained when the antibrain-type phosphorylase isoenzyme antibody was used, but not when the other two types were used. The results suggest that brain-type phosphorylase in gastric carcinoma could be one example of fetal protein expression in cancer, and that the proliferative zone of some intestinal metaplasia having brain-type phosphorylase may histogenetically relate to well-differentiated adenocarcinoma.

Histochemical Study of Phosphorylase in Proliferating Cells of Intestinal Metaplasia and Carcinoma of the Human Stomach

A morphologic histochemical study of phosphorylase was carried out to investigate the relationship between gastric carcinoma and intestinal metaplasia. Intense phosphorylase activity was observed in the carcinoma cells, especially in well-differentiated adenocarcinoma, and in the proliferating cells of some intestinal metaplasias. Metaplastic epithelium other than the proliferating cells occasionally showed a positive reaction. Phosphorylase was negative in normal gastric epithelium, even in its proliferating cells. There was an apparent coincidence between the location of well-differentiated adenocarcinoma and the distribution of intestinal metaplasia, with the proliferating cells showing positive reaction for phosphorylase. These data suggest that the relationship between the proliferating cells of intestinal metaplasia showing phosphorylase activity and well-differentiated adenocarcinoma is apparently closer than the much-debated relationship between the epithelium of intestinal metaplasia and gastric carcinoma.